The Effect of Epidural Analgesia on Maternal and Early Neonatal Outcomes: A Retrospective Cohort Study in Qatar

Article Information

Ismail Sabry Abdelhady, Elsayed Ibrahim Salama*, Sabry Naser Ahmed, Alaa Masry, Ashraf Gad

Division of Neonatal-Prenatal Medicine, Women’s Wellness and Research Centre, NICU, Hamad Medical Corporation, Weill Cornel Medicine, Qatar

*Corresponding Author: Elsayed Ibrahim Salama, Division of Neonatal-Prenatal Medicine, Women’s Wellness and Research Centre, NICU, Hamad Medical Corporation, Weill Cornel Medicine, Qatar.

Received: 20 March 2023; Accepted: 28 March 2023; Published: 30 March 2023

Citation:

Ismail Sabry Abdelhady, Elsayed Ibrahim Salama, Sabry Naser Ahmed, Alaa Masry, Ashraf Gad. The Effect of Epidural Analgesia on Maternal and Early Neonatal Outcomes: A Retrospective Cohort Study in Qatar. Journal of Pediatrics, Perinatology and Child Health 7 (2023): 55-65.

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Abstract

Objective: Epidural Analgesia (EA) is commonly used method to alleviate labor pain. In the present study, we aimed to describe the maternal and neonatal morbidities associated with EA.

Methods: A retrospective cohort data analysis of the PEARL-Peristat Study. Our sample consisted of a total of 7721 singleton vaginal births occurred at the Woman’s hospital between January 2017 and April 2018. Pregnancy characteristics and maternal and neonatal outcomes were compared between the two groups. Regression analysis was constructed to identify factors associated with the use of EA.

Results: Out of the total participants, 2969 women (38.5%) received epidural analgesia (EA) during labor. Several maternal and pregnancy factors were significantly associated with the use of EA, including Qatari nationality (adjusted odds ratio (aOR) 1.31, 95% confidence interval (CI) 2.10 (1.81-2.44), p<0.001), low parity (aOR 0.79 (0.66-0.96), p=0.017), vaginal birth after Cesarean (aOR 1.92 (1.51-2.45), p<0.001), labor induction (aOR 1.60 (1.39-1.85), p<0.001), prolonged first stage of labor (aOR 1.01 (1.01-1.02), p<0.001), and prolonged second stage of labor (aOR 1.01 (1.01-1.02), p<0.001). Among maternal and neonatal outcome variables, intrapartum fever (aOR 4.43 (1.47-13.38), p=0.008), instrumental delivery (aOR 4.43 (1.47-13.38), p=0.003), and reduced risk of meconium stained amniotic fluid (aOR 0.74 (0.55-0.99), p=0.040) were significantly associated with EA use during labor.

Conclusion: The study identified key factors associated with EA use during labor, including nationality, parity, birth type, labor stages, and specific maternal and neonatal outcomes. Further research is needed to better understand these associations and optimize EA use in labor management.

Keywords

Epidural Analgesia; Labour; Nulliparous; Qatari; Outcome; Neonate; Pregnancy

Epidural analgesia articles, Labour articles, Nulliparous articles, Qatari articles, outcome articles, neonate articles, pregnancy articles

Article Details

1. Introduction

Epidural Analgesia (EA), is a type of Neuroaxial Analgesia (NA) currently used by obstetricians to effectively reduce labor pain [1]. In recent years, the use of EA has increased significantly, with estimates ranging from 20–70% of all deliveries [2-6]. Absolute contraindications to NA are infrequent, while relative contraindications encompass coagulopathy, lower back infection, and increased intracranial pressure associated with intracranial pathology. Compared to parenteral opioids, EA provides significantly more analgesia, as measured by a visual analog scale in both the first and second stages of labour [7]. There is continuing controversy over whether EA impedes the progress of labor by causing dystocia and increasing the operative delivery rate, despite the association of NA with the reduction of anesthesia-related maternal mortality [8-10]. Several studies have described various adverse effects among pregnant women users of EA, such as a rise in body temperature, difficulty in the onset of lactation, hypotension, the prolonged second stage of labor, and an increase in instrumental vaginal delivery [1,6,11-15]. In some studies, EA has been suggested to potentially influence neonatal outcomes, leading to low Apgar scores and decreased umbilical arterial pH values. However, systematic reviews have not established a connection between the utilization of EA and an increase in Neonatal Morbidity [NM] [1,6,7,16-18]. Another recent findings indicate the impacts of NA on the risk of cesarean delivery, the length of labor, breastfeeding success, and pre-existing or new-onset low back pain have been largely reassuring [19]. In light of the conflicting research results concerning the outcomes of EA during labor, the primary objective of this study is to describe the maternal and neonatal morbidities associated with EA.

2. Methods

2.1 Study design

This was a retrospective cohort data analysis of the PEARL-Peristat Study data [Perinatal Neonatal Outcomes Research Study in the Arabian Gulf] Qatar. The PEARL-Peristat Study was a registry-based study designed to study immediate and long-term pregnancy outcomes of births using routinely collected hospital data. The study was funded by Qatar National Research Fund [Grant no. NPRP 6-238-3-059] and sponsored by the Medical Research Centre, Hamad Medical Corporation (HMC). The study was approved by the HMC Institutional Review Board [IRB], with a waiver of consent [HMC-IRB 13064/13].

2.2 Setting and participants

The sample for this study comprised of births from January 2017 and April 2018 conducted at the Women’s Hospital [WH] [now known as the Women’s Wellness and Research Center (WWRC)], in Qatar. As the largest governmental-operated tertiary hospital, this sample is generally representative of most births in the country. For this study, we retrieved 20625 singleton vaginal births from 24 weeks gestation and above. We then excluded babies with major congenital abnormalities, stillbirths, immediate neonatal death in the labor room or operating theatre, birth weights <2500g or >4000g, gestational age <37 weeks or >41+6 weeks, women with diabetes and hypertension, precipitate labor (defined as total labor duration less than 180 minutes, and other missing data [20]. We, therefore, analyzed 7721 births after exclusion as described above.

2.3 Comparison group

Women who received EA were compared to women without EA in labor.

2.4 Covariates and outcomes

Maternal: Explanatory factors included maternal age, parity grouped into nulliparous or greater than or equal to one parous experience and nationality was grouped into Qatari and no-Qatari. In addition, we examined the use of opioid analgesia [morphine] in labor and calculated the Body Mass Index [BMI] at delivery. Maternal outcomes studied included suspected chorioamnionitis, meconium-stained amniotic fluid [MSAF], labor duration [first stage, second stage, and third stage], instrumental delivery using vacuum or forceps, postpartum hemorrhage and admission to intensive care unit.

Newborn: These included Gestational Age (GA), Birth Weight (BW) and gender. Immediate outcomes included arterial and venous cord PH, Apgar score less than 7 at 1 and 5 minutes, admission to the Neonatal Intensive Care [NICU]. In addition, NICU admission reason such as respiratory distress and suspected sepsis. Other variables were birth trauma and in-hospital mortality. Birth trauma included caput succedaneum, subgaleal hematoma, cephalohematoma, brachial plexus injury, clavicular fracture, facial nerve injuries, and subconjunctival hemorrhage.

2.5 Statistical analysis

We summarized the distribution of variables using numbers and percentages, mean and standard deviation or median and interquartile ranges as appropriate. Based on the data type, we compared the proportions and the incidence of the study covariates and outcomes between the EA and control groups using either chi-square tests, Fishers’ test or Mann-Whitney U test. Both univariate and multivariate logistic regression analyses were performed to account for potential confounding variables associated with EA. Statistical analysis was performed using IBM SPSS 26 [SPSS Inc., Chicago, IL, USA] statistical software with statistical significance set at p<0.05.

3. Results

The study group comprised 7721 nulliparous and multiparous women, 2969 women received EA (38.45%) while 4752 women did not received EA.

Table 1 shows the comparison of socio-demographic variables between the 2 groups. Mother received EA were younger in age than those who did not receive EA, also use of Opioid analgesia was significantly lower in the EA group [p < 0.001]. BMI was higher in EA group, nulliparous and Qatari women were more prevalent to receive EA [p<0.001]. Conversely, the proportion of multiparous women who received EA was significantly lower (p < 0.001).

Epidural Analgesia

Total

No

Yes

[n=7721]

[n=4752]

[n=2969]

p-value

n

%

n

%

n

%

Maternal age*

28.12 ± 5.22

28.44 ± 5.25

27.61 ± 5.14

<0.001

BMI at delivery*

30.26 ± 5.14

30 ± 5.09

30.68 ± 5.2

<0.001

Parity

 <0.001

 Nullipara

2450

0.317

1074

0.226

1376

0.463

 Parity ≥1

5271

0.683

3678

0.774

1593

0.537

Nationality

<0.001

 Non-Qatari

5317

0.689

3471

0.73

1846

0.622

 Qatari

2404

0.311

1281

0.27

1123

0.378

Opioid analgesia

<0.001

 No

6100

0.79

3414

0.718

2686

0.905

 Yes

1621

0.21

1338

0.282

283

0.095

*Values are expressed as “Mean ± SD”

Table 1: Maternal demographic variables of both groups.

Epidural Analgesia

Total

No

Yes

p-value

[n=7721]

[n=4752]

[n=2969]

n

%

n

%

n

%

Intrapartum fever

No

7602

0.985

4725

0.994

2877

0.969

Yes

119

0.015

27

0.006

92

0.031

<0.001

VBAC

No

7160

0.927

4443

0.935

2717

0.915

Yes

561

0.073

309

0.065

252

0.085

0.001

Clinical chorioamnionitis

No

7620

0.987

4726

0.995

2894

0.975

Yes

101

0.013

26

0.005

75

0.025

<0.001

Membrane rupturea

<18hrs

7071

0.918

4479

0.944

2592

0.876

≥18hrs

631

0.082

265

0.056

366

0.124

<0.001

MSAF

No

6504

0.843

4040

0.851

2464

0.83

Yes

1209

0.157

706

0.149

503

0.17

0.015

Instrumental Delivery

No

6999

0.906

4539

0.955

2460

0.829

Yes

722

0.094

213

0.045

509

0.171

<0.001

PPH

No

7323

0.948

4593

0.967

2730

0.92

Yes

398

0.052

159

0.033

239

0.08

<0.001

1st stage of labor [mins] a

300 [230-386]

270 [220-345]

345 [270-448]

<0.001

2nd stage of labor [mins] a

15 [6-48]

10 [5-22]

43 [15-112]

<0.001

3rd stage of labor [mins] a

5 [5-7]

6 [5-8]

5 [5-7]

<0.001

Total labor duration [mins] a

330 [255-445]

295 [237 - 375]

415 [320-540]

<0.001

a =Missing data: membrane rupture [n=19], 1st stage of labor [n= 9], 2nd stage of labor [n=55], 3rd stage of labor [n=100], total duration of labor [n=2]. Labor data reported in median and interquartile range [IQR], VBAC; vaginal birth after caesarean, MSAF; meconium stained amniotic fluid, PPH; postpartum hemorrhage

Table 2: Pregnancy Outcomes in both groups.

Table 2 presents a comparison of maternal clinical outcomes between the two groups. The outcome measures include intrapartum fever, VBAC [vaginal birth after cesarean], chorioamnionitis, amniotic membrane rupture ≥ 18 hr [PROM] before one of birth, instrumental delivery, PPH [ post-partum hemorrhage], and MSAF occurred significantly more frequently in mothers who received EA compared to those in the control group. Additionally, different stages of labor were compared between the two groups, the first and second stages, in addition to the total duration of labor (mins) were all prolonged in the EA group compared to the control group, however, the duration of the second stage of labor was shorter in the EA group.

Neonatal clinical characteristics and outcomes are presented in Table 3, many variables were higher in the EA group [p<0.001, <0.005] like GA, total NICU admission rates, birth trauma, NICU admission for suspected sepsis [p<0.001], and respiratory distress is higher in the EA [p=0.003]. Cord venous and arterial pH is lower in the EA [p<0.001and p<0.002]. There was no statistical difference between both groups in Apgar < 7 at 1 min and at 5 min [p=0.686 and p= 0.636]. No statistical difference was observed between both groups in BW [p=0.067] and gender [p=0.565]. There were no differences in later neonatal mortalities between the two groups.

Epidural Analgesia

Total

No

Yes

p-value

[n=7721]

[n=4752]

[n=2969]

n

%

n

 %

n

%

Birth weight*

3252.3 ± 343.9

3246.6 ± 341.5

3261.4 ± 347.8

0.067

Gestational age*

39.20 ± 1.08

39.16 ± 1.07

39.25 ± 1.10

<0.001

Cord arterial pH a*

7.29

0.1

7.29

0.1

7.28

0.09

0.002

Cord venous pH a*

7.32

0.09

7.33

0.09

7.31

0.08

<0.001

NICU admission

No

7357

0.953

4581

0.964

2776

0.935

Yes

364

0.047

171

0.036

193

0.065

<0.001

NICU admission for suspected sepsis

No

7506

0.972

4662

0.981

2844

0.958

Yes

215

0.028

90

0.019

125

0.042

<0.001

NICU admission for respiratory distress

No

7623

0.987

4706

0.99

2917

0.982

Yes

98

0.013

46

0.01

52

0.018

0.003

Gender

Male

3887

0.503

2380

0.501

1507

0.508

Female

3834

0.497

2372

0.499

1462

0.492

0.565

Apgar <7 at 1min

No

7665

0.993

4719

0.993

2946

0.992

Yes

56

0.007

33

0.007

23

0.008

0.686

Apgar <7 at 5mins

No

7716

0.999

4749

0.999

2967

0.999

Yes

5

0.001

3

0.001

2

0.001

0.636

Birth Trauma

No

7658

0.992

4724

0.994

2934

0.988

Yes

63

0.008

28

0.006

35

0.012

0.005

Newborn Outcome

Discharged alive

7717

0.999

4748

0.999

2969

1

In-hospital mortality

4

0.001

4

0.001

0

0

NA

a = Missing data: Cord arterial pH [n=6551], cord venous pH [n= 6605]
*Data reported as mean and SD. NA= not applicable

Table 3: Neonatal clinical characteristics and outcomes in both groups.

To identify factors associated with EA, both univariate and multivariate logistic regression analyses were performed to account for potential confounding variables. These variables included maternal and pregnancy factors, as well as maternal and neonatal outcomes (Table 4). Maternal and pregnancy factors included maternal age, conception mode (artificial vs. natural), nationality, VBAC, parity, baby gender, gestational age, PROM, labor stages duration, labor induction using prostaglandin, maternal weight, height, and BMI at delivery.

After adjusting for these variables, Qatari nationality (adjusted odds ratio (aOR) 1.31, 95% CI 2.10 (1.81-2.44), p<0.001), parity (aOR 0.79 (0.66-0.96), p=0.017), VBAC (adjusted OR 1.92 (1.51-2.45), p<0.001), labor induction (aOR 1.60 (1.39-1.85), p<0.001), prolonged first stage of labor (aOR 1.01 (1.01-1.02), p<0.001), and prolonged second stage of labor (aOR 1.01 (1.01-1.02), p<0.001) were significantly associated with EA. Maternal and neonatal outcome variables (Table 4) included postpartum hemorrhage, chorioamnionitis, intrapartum fever, instrumental delivery, MSAF, cord arterial pH and base-deficits, low Apgar score at 1 minute, birth trauma, and NICU admission for respiratory distress or sepsis. After adjusting for other variables, the study found that intrapartum fever (aOR 4.43 (1.47-13.38), p=0.008), instrumental delivery (aOR 4.43 (1.47-13.38), p=0.003), and less risk of MSAF (aOR 0.74 (0.55-0.99), p=0.040) were significantly associated with EA during labor. 

Maternal and pregnancy characteristics: Epidural vs. no epidural analgesia

Variables

unadjusted OR (95%CI)

p-value

adjusted OR (95%CI)*

p-value

Maternal age

0.70 (0.60−0.82)

<0.001

0.99 (0.81−1.23)

0.988

Maternal weight at delivery

1.01 (1.01−1.02)

<0.001

1.02 (0.95−1.10)

0.532

Maternal BMI

1.03 (1.02−1.04)

<0.001

0.96 (0.80−1.15)

0.663

Maternal height

1.02 (1.01−1.03)

<0.001

0.99 (0.92−1.07)

0.895

Conception mode, ART

2.12 (1.42−3.17)

<0.001

1.77 (0.98−3.18)

0.057

Nationality, Qatari

1.81 (1.63−2.02)

<0.001

2.10 (1.81−2.44)

<0.001

Parity

0.37 (0.34−0.42)

<0.001

0.79 (0.66−0.96)

0.017

VBAC

1.43 (1.18−1.73)

<0.001

1.92 (1.51−2.45)

<0.001

Membranes ruptured ≥18hr

2.16 (1.79−2.59)

<0.001

1.10 (0.82−1.47)

0.517

Labor induction

1.99 (1.76−2.25)

<0.001

1.60 (1.39−1.85)

<0.001

First stage of labor, duration

1.03 (1.02−1.03)

<0.001

1.01 (1.01−1.02)

<0.001

Second stage of labor, duration

1.02 (1.01−1.02)

<0.001

1.01 (1.01−1.02)

<0.001

Third stage of labor, duration

1.00 (0.99−1.02)

0.899

1.00 (0.99−1.01)

0.629

Gestational age

1.07 (1.02−1.12)

0.003

1.03 (0.96−1.10)

0.486

Birth weight

0.95 (0.99−1.00)

0.019

1.00 (0.99−1.00)

0.095

Female gender

0.94 (0.86−1.04)

0.263

0.90 (0.78−1.03)

0.136

Maternal and neonatal outcomes: Epidural vs. no epidural analgesia

Variables

unadjusted OR (95%CI)

p-value

adjusted OR (95%CI)#

p-value

PPH

1.92 (1.55 −2.39)

<0.001

1.06 (0.67−1.67)

0.807

Chorioamnionitits

2.85 (1.82 −4.45)

<0.001

0.52 (0.17−1.60)

0.253

Intrapartum fever

3.47 (2.26−5.32)

<0.001

4.43 (1.47−13.38)

0.008

Instrumental delivery

3.18 (2.67−3.77)

<0.001

1.63 (1.18−2.26)

0.003

MSAF

1.18 (1.03−1.35)

0.017

0.74 (0.55−0.99)

0.04

Cord arterial pH

0.37 (0.10−1.39)

0.142

0.87 (0.19−4.08)

0.863

Cord arterial based deficit

0.98 (0.96−1.01)

0.313

1.002 (0.97−1.03)

0.903

Low 1 minute Apgar score

2.91 (1.37−6.19)

0.005

2.29 (0.74−7.03)

0.149

Birth trauma

1.85 (1.05−3.26)

0.034

1.16 (0.40−3.32)

0.787

NICU for respiratory distress

1.67 (1.09 −2.57)

0.018

0.72 (0.29−1.74)

0.462

NICU for suspected sepsis

1.80 (1.34 −2.41)

<0.001

1.09 (0.47−2.51)

0.84

OR, odds ratio; CI, confidence interva; BMI, body mass index; ART, assisted reproductive technologies; VBC, vaginal birth after Cesarean; PPH, postpartum hemorrhage; MSAF, meconium stained amniotic fluid
*adjusted for other variables in material and pregnancy characteristics group
#adjusted for all other variables in maternal and neonatal outcomes group

Table 4: Regression analysis of variables associated with use of epidural analgesia during labor.

4. Discussion

For reducing pain during labor, EA appears to be effective in this aspect. Due to conflicting results in the literature about this particular topic, our study aimed to describe the maternal and neonatal morbidities associated with EA in a large tertiary care center where 38.5% of the participants received EA during labor. The results of our study indicate that several maternal, pregnancy, and neonatal factors were significantly associated with the use of EA during labor. The results of this study revealed that several maternal and pregnancy variables were significantly linked to the use of EA, including Qatari nationality, lower parity, VBAC, labor induction, prolonged first and second stages of labor. Additionally, intrapartum fever, instrumental delivery, and a reduced risk of MASF were also found to be associated with EA use. However, after controlling for confounding variables, the study did not identify independent associations between certain outcomes such as birth trauma, low cord pH, low Apgar scores, or NICU admission for sepsis, chorioamnionitis, or respiratory distress and the use of EA in labor. This suggests that these outcomes may be influenced by other factors that are not related to EA use. In concordance with our study, one study compared the two groups in terms of socio-demographic data, the duration of the second stage of labor was prolonged in women received EA [33.13 ± 12.78 min], as compared to the control [27.53 ± 11.73 min]. On the contrary, the same study showed that the first stage of labor was shorter in the EA [4.83 ± 1.59 h] compared to the control group [5.48 ±1.56 h], and instrumental vaginal or cesarean delivery rates did not increase in patients received EA [21]. Another study found that EA and prolonged second stage of labor duration are not related to the neonatal morbidity, while the instrumental delivery doubles the risk of neonatal morbidity compared to the normal vaginal delivery. The authors therefore concluded that the second stage of labor does not need to be terminated for the duration alone [22,23]. Recent studies suggested that, although the duration of the second stage of labor is associated with increased risks of certain adverse maternal outcomes, there is no relationship between the duration of the second stage and adverse neonatal outcomes. However, most studies on this issue are from single centers [24-26]. For another aspect, one study showed that EA increases NICU admission, antibiotic exposure, neonatal birth injuries, need for positive pressure ventilation at birth, and respiratory distress in the first 24 hours of life. Moreover, mothers who received EA, had a longer second stage, temperature elevation >37.5°C, and subjected to more instrumental delivery [6,27]. A recent study from Qatar showed similar findings to ours with regards to EA being related to a prolonged second stage of labor and increased rate of instrumental delivery. However, our study found a negative association to MSAF. Additionally, in this study, we did not observe an independent association between fetal distress, or birth trauma and EA [27]. Previous single-center studies have found conflicting results regarding the contribution of maternal EA to neonatal administration of antibiotics [28,29]. One of the major clinical criteria for sepsis evaluation is maternal intrapartum fever. However, EA can also lead to maternal fever and is not associated with an increased risk of infection in the neonate, thus leading to unnecessary neonatal exposure to antibiotics [30]. Among a large cohort of mother-neonate pairs across the state of Colorado over 6 years, EA was associated with a 26% increased odds of neonatal exposure to antibiotics. Although mothers who received EA were 5 times more likely to have a fever, the proportion of neonates treated with antibiotics did not differ by EA status. This result supports the hypothesis that EA is a risk factor for noninfectious maternal fevers, but neonates born to mothers with fever were treated without respect to whether the mother had an EA [31]. In other studies, it was found that EA is associated with increased rates of maternal intrapartum fever [29,32-34]. However, the relationship between EA, maternal fever, and neonatal antibiotic treatment has been limited to conflicting single-center studies at academic, and tertiary care institutions. Goetzl et al. [28] conducted a follow-up study of a cohort of 1934 births which demonstrated that in mothers with low grade [<37.5°C] or no fever, EA was associated with a three-fold increased risk of sepsis evaluation in neonates as well as increased rates of neonatal antibiotic treatment [28]. In contrast, Kaul et al. [29] found no association between EA and neonatal sepsis evaluation in 1177 primiparous births at Magee-Women’s Hospital, Pittsburg, Pennsylvania, USA [29]. Our results showed that cord venous and arterial pH values were lower in the EA group. However, no statistically significant associations were observed between cord pH values and EA after controlling for other variables, similar to low Apgar scores at 1 minute and 5 minutes. This finding is consistent with several previous studies that found no significant differences in neonatal outcomes between the EA and control groups [7,21,27,35-37]. In a Cochrane review by Anim-Somuah et al. [28], EA did not appear to have an immediate effect on neonatal status as determined by the Apgar score, with an OR of 0.70 [, 95% CI 0.44–1.10] for an Apgar score of < 7 after EA [28]. However, other studies reported a higher incidence of low Apgar score in the EA group and higher needs for neonatal resuscitation among women who received EA [29,37,38].

5. Conclusion

The study showed that several maternal and pregnancy variables, such as Qatari nationality, lower parity, VBAC, labor induction, and prolonged first and second stages of labor, were significantly related to the use of EA. Additionally, maternal and neonatal outcomes variables, such as intrapartum fever, instrumental delivery, and reduced risk of MASF, were also found to be associated with EA use. However, the study did not find independent associations between certain outcomes, such as birth trauma, low cord pH, low Apgar scores, or NICU admission for sepsis or respiratory distress, and the use of EA in labor. This highlights the need for obstetricians to provide balanced and comprehensive information on EA to pregnant women considering this option. Given the limited information on the effect of opioid analgesia on labor pain in association with EA, it may be beneficial to conduct further studies in this area.

The study's limitations include its retrospective design, which may introduce selection bias, and the potential for unmeasured confounding factors. Additionally, the single-center setting may limit the generalizability of the findings to other populations. Furthermore, some data points were missing for certain variables, which may impact the analysis and conclusions. The study also focuses on short-term outcomes, limiting its ability to assess long-term effects. Lastly, the presence of other confounding variables not accounted for in the study may influence the observed associations.

Conflict of iInterest

Each author declares that he or she has no commercial associations [e.g. consultancies, stock ownership, equity interest, patent/licensing arrangement etc.], that might pose a conflict of interest in connection with the submitted article.

Acknowledgments:

Qatar National research fund for its support to produce and fund such a wealthy maternal-newborn registry in the State of Qatar.

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