Perinatal health features of children born with the help of reproductive technologies

G. V. Lundina; Лундина Г. В.; V. S. Koryagin; Корягин В. С.; Е. A. Pesterev; Пестерев Е. А.; V. V. Vanyukov; Ванюков В. В.; A. S. Zagumennov; Загумённов А. С.; A. A. Nurislamova; Нурисламова А. А.; P. K. Penkova; Пенькова П. К.; Z. V. Zheludkov; Желудков З. В.; D. A. Iksanov; Иксанов Д. А.

doi:10.17816/pmj42129-35

Perinatal health features of children born with the help of reproductive technologies

Authors: Lundina G.V.¹, Koryagin V.S.¹, Pesterev Е.A.¹, Vanyukov V.V.¹, Zagumennov A.S.¹, Nurislamova A.A.¹, Penkova P.K.¹, Zheludkov Z.V.¹, Iksanov D.A.¹
Affiliations:
1. Ye.A. Vagner Perm State Medical University
Issue: Vol 42, No 1 (2025)
Pages: 29-35
Section: Original studies
Submitted: 03.10.2024
Published: 13.03.2025
URL: https://permmedjournal.ru/PMJ/article/view/636677
DOI: https://doi.org/10.17816/pmj42129-35
ID: 636677

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Abstract

Objective. To assess the health indicators of infants born as a result of natural conception and those born using assisted reproductive technology – in vitro fertilization (IVF).

Materials and methods. Birth and development histories of 25 premature babies have been studied. All of them had been conceived with IVF and were in therapy in the Department of Pathology of newborns and premature infants of Children's Clinical Hospital №13, Perm. In a “case–control” study 2 groups of children were studied, group 1 consisted of babies born through IVF; group 2 – children born as a result of pregnancy that occurred naturally, then the health of these groups was investigated (according to certain data), next the results of the investigation were compared between the two groups. In both groups, obstetric and gynecological history data, Apgar scale indicators were studied, newborns’ body weight, cerebral ischemia were assessed, and biochemical parameters such as total bilirubin, alkaline phosphatase, gamma-glutamyltranspeptidase were analyzed. The absolute values are calculated in the form of the arithmetic mean (M) and the standard deviation (SD). Statistical processing was carried out with StatSoft Statistica 12.6 software, using the nonparametric Mann – Whitney U-test as the data distribution differs from the normal one. Statistically significant differences were considered at p < 0.05.

Results. It was determined that the proportion of infants with very low body weight (BMI) was higher in the IVF group – 24.0 % (6 children) compared to the control group, where the number of those was 5.0 % (1 child), but these differences did not reach the level of statistical significance (p>0.05). Apgar score on the 5^th minute of life, as well as at birth, in the group of newborns conceived with IVF, was validly higher – 8.24 ± 0.09 points opposite to 8.10 ± 0.12 points in children born as a result of natural pregnancy (p<0.05). The analysis of frequency of pathological conditions in newborns showed that there were no significant differences between the groups (p>0.05).

Conclusions. Children conceived through assisted reproductive technology IVF are more likely to be born with very low body weight than babies conceived naturally. Anthropometric characteristics and Apgar score do not differ from those of children born as a result of natural conception. In the newborn period, they have more pronounced cholestasis syndromes, however both groups are comparable in terms of the incidence of the main newborn pathologies. Thus, it cannot be stated that children conceived through IVF are much inferior in health criteria to those infants who were conceived and born naturally.

Keywords

IVF, perinatal features of children, born from the first birth, pediatrics, health status of newborns

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Introduction

In vitro fertilization is currently the most advanced method of combating infertility, the efficiency of this technology is 35–37 % [1–4]. Over the last 30 years more than 5 million children worldwide have been born as the result of this procedure. The number of children born through assisted reproductive technologies continues to grow, according to the statistics, they make up more than 1 % of all newborns [5–7]. It has been statistically proven that children born as a result of the IVF procedure, have more health problems, while naturally conceived newborns are generally healthier [8–9]. However, there are also researches contradicting this conclusion, making further investigation of the issue relevant.

The objective of the study is to assess the health indicators of infants born from natural conception and those born using assisted reproductive technology – in vitro fertilization.

Materials and Methods

The study analyzed delivery records and medical histories of 25 premature babies. All conceived through in vitro fertilization (IVF) and treated in the department of pathology of newborns and premature infants at Perm Regional Children’s Clinical Hospital No.13, Perm, Russia. Criteria for inclusion in the main group:

Infants born through IVF conception;
Premature pregnancy (22–36 weeks);
First-born infants (mother’s first delivery).

Criteria for exclusion from the main group:

Naturally conceived and delivered infants;
Full-term pregnancy (38 weeks and more);
Infants born from the second and subsequent pregnancies.

A case-control study: two groups of children were studied, group 1 (main group) included children born using IVF; group 2 (control group) included children born as a result of pregnancy that occurred naturally, then the health of children of these groups was studied (according to certain data), then the results of the study of the two groups were compared. In both groups the obstetric and gynecological history, Apgar scale indicators were studied, the birth weight, presence of cerebral ischemia were assessed, and biochemical indicators were analyzed: total bilirubin, alkaline phosphatase, gamma-glutamyl transpeptidase.

Absolute indicators were calculated as the arithmetical mean (M) and standard deviation (SD). Statistical processing was performed using StatSoft Statistica 12.6, the non-parametric Mann–Whitney U-test was used due to the fact that the data distribution differs from the normal ones. The differences were considered statistically significant at p < 0.05.

Results and Discussion

The average age of women treated for infertility with IVF was 35.0 ± 1.0 years, compared to 26.9 ± 1.1 years in the control group. In patients of the IVF program group, the frequency of multiple pregnancies was significantly higher – 64.0 %, in the control group – 25.0 % (p < 0.05). According to the features of the obstetric and gynecological history (Table 1), IVF patients, more often than those, who conceived naturally, had abortions (24 %), ectopic pregnancies (28 %), miscarriages (16 %), sexually transmitted infections (28 %), of the total number of complications. Naturally conceived pregnancies were associated with fewer complications.

Table 1 Features of patients’ obstetric and gynecological history

Complications in the anamnesis	Main group, n = 25		Control group, n = 20		p
Complications in the anamnesis	n	%	n	%	p
Abortions	6	24	4	20	> 0.05
Ectopic pregnancy	7	28	0	0	< 0.05
Miscarriage	4	16	1	5	> 0.05
Sexually transmitted infections	7	28	2	10	> 0.05

No significant differences in birth rates were found at 29^th–30^th, 31^st–33^rd, and 34^th–36^th weeks (Table 2). The hypothetical risk of premature birth is just as high in those who conceive naturally as in those who use assisted reproductive technology.

Table 2 Features of delivery timing

Delivery timing, number of weeks	Main group, n = 25		Control group, n = 20		p
Delivery timing, number of weeks	n	%	n	%	p
29–30	6	24.0	1	5.0	> 0.05
31–33	4	16.0	7	35.0	> 0.05
34–36	15	60.0	12	60.0	> 0.05

The proportion of infants with very low birth weight (VLBW) was higher in the IVF group – 24.0 % (n = 6) vs 5.0 % (n = 1) of the control group of newborns, but the difference was not statistically significant (p > 0.05). The number of low birth weight (LBW) infants was 76.0 % (n = 19) and 95.5 % (n = 19), respectively, at p > 0.05. It was noted that the birth weight of children in the main group did not differ significantly from that of the control group – 2078.8 ± 123.3 g vs 2081.9 ± 88.3 in the control group (p > 0.05). No significant difference in birth length was found between the infants of the two groups. At birth the infants` body length in the main group was – 44.1 ± 0.9 cm, in the control group it was almost equal – 44.2 ± 0.6 cm (p > 0.05). The assessment according to the Apgar scale at the 5^th minute of birth in the cohort of children conceived as a result of IVF, as well as at the time of birth, was significantly higher – 8.24 ± 0.09 points vs 8.10 ± 0.12 in infants, born as a result of natural pregnancy (p < 0.05).

Analysis of total bilirubin (TB) levels revealed that in the main group on the 1st day of life TB levels were higher with a content of 94.7 ± 13.5 μmol /l vs 92.6 ± 12.5 in the control group (p < 0.05). In newborns from natural conception, a sharp increase in the bilirubin level was noted on the 6th day of life, as a result of which it was 35 μmol/l higher than that of infants born after using IVF technology (p < 0.05). On the 21st day from the moment of birth, a drop in indicators occurred: the average level of total bilirubin was 11 μmol/l lower than the value in the control group (p < 0.05). The alkaline phosphate (ALP) parameter was significantly higher in children of the main group – 930.0 ± 77.1 U/l vs 916.4 ± 88.1 in the control group (p < 0.05), the gamma-glutamyl transpeptidase (GGTP) level was also higher – 141.1 ± 25.7 U/l vs 97.8 ± 7.4, respectively (p < 0.05).

The analysis of the frequency of pathological conditions in newborns (Table 3) revealed that the prevalence of jaundice without cholestasis was quite high in both groups. It occurred in more than 3/4 of children in both compared cohorts, while statistical significance was not found (p > 0.05). There were no significant differences in the incidence of jaundice with cholestasis as well, it being revealed in 32.0 % of IVF infants and in 25.0 % of infants from the natural conception group (p > 0.05). Respiratory distress syndrome and retinopathy of the newborn affected approximately one third of children from both groups (p > 0.05).

Тable 3 Assessment of pathological conditions of newborns

Pathology	Main group, n = 25		Control group, n = 20		p
Pathology	n	%	n	%	p
Jaundice without cholestasis	17	68.0	15	75.0	> 0.05
Jaundice with cholestasis	8	32.0	5	25.0	> 0.05
Intrauterine infection	16	64.0	11	55.0	> 0.05
Retinopathy	9	36.0	8	40.0	> 0.05
Respiratory distress syndrome	8	32.0	6	30.0	> 0.05
Intrauterine growth restriction	5	20.0	2	10.0	> 0.05

The assessment of the cerebral ischemia (CI) degree showed that both groups were practically indistinguishable in the occurrence of this pathology. The most common was the CI of the 1st degree: it was registered in 64.0 % of newborns in the main cohort and in 60.0 % of infants in the control group (p > 0.05); the 2nd degree of CI was diagnosed in 36.0 % of children in the main group and in 40.0 % of the control group (p > 0.05).

Conclusions

Children conceived through such assisted reproductive technology as IVF are more often born with very low birth weight than infants conceived naturally. Anthropometric characteristics and Apgar scores do not differ from those of children born as a result of natural conception. In the neonatal period, they have more pronounced cholestasis syndromes, but in terms of the frequency of the main pathologies of the neonatal period, both groups are comparable. Therefore, it cannot be stated that children conceived through IVF are significantly inferior in terms of health criteria to those infants who were conceived and born naturally.